Research Papers:

Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase

Marta Lualdi, Edoardo Pedrini, Katia Rea, Laura Monti, Debora Scaldaferri, Marzia Gariboldi, Annalisa Camporeale, Paolo Ghia, Elena Monti, Antonella Tomassetti, Francesco Acquati _ and Roberto Taramelli

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Oncotarget. 2015; 6:7851-7865. https://doi.org/10.18632/oncotarget.3490

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Marta Lualdi1, Edoardo Pedrini1, Katia Rea2, Laura Monti1, Debora Scaldaferri1, Marzia Gariboldi3, Annalisa Camporeale4,6, Paolo Ghia4,5, Elena Monti3, Antonella Tomassetti2, Francesco Acquati1 and Roberto Taramelli1

1 Department of Theoretical and Applied Sciences, Università degli Studi dell’Insubria, Varese, Italy

2 Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

3 Department of Theoretical and Applied Sciences, Università degli Studi dell’Insubria, Busto Arsizio, Italy

4 Division of Molecular Oncology and Department of Onco-Hematology, IRCCS Ospedale San Raffaele, Milan, Italy

5 Università Vita-Salute San Raffaele, Milan, Italy

6 Present address: Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Turin, Italy

Correspondence to:

Francesco Acquati, email:

Keywords: RNase, Ovarian cancer, Microenvironment, Stress response

Received: December 01, 2014 Accepted: February 02, 2015 Published: March 08, 2015


As widely recognized, tumor growth entails a close and complex cross-talk among cancer cells and the surrounding tumor microenvironment. We recently described the human RNASET2 gene as one key player of such microenvironmental cross-talk. Indeed, the protein encoded by this gene is an extracellular RNase which is able to control cancer growth in a non-cell autonomous mode by inducing a sustained recruitment of immune-competent cells belonging to the monocyte/macrophage lineage within a growing tumor mass. Here, we asked whether this oncosuppressor gene is sensitive to stress challenges and whether it can trigger cell-intrinsic processes as well. Indeed, RNASET2 expression levels were consistently found to increase following stress induction. Moreover, changes in RNASET2 expression levels turned out to affect several cancer-related parameters in vitro in an ovarian cancer cell line model. Of note, a remarkable rearrangement of the actin cytoskeleton organization, together with changes in cell adhesion and motility, emerged as putative mechanisms by which such cell-autonomous role could occur. Altogether, these biological features allow to put forward the hypothesis that the RNASET2 protein can act as a molecular barrier for limiting the damages and tissue remodeling events occurring during the earlier step of cell transformation.

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